Study of surgical indication for knee arthroplasty by cartilage analysis in three compartments using data from Osteoarthritis Initiative (OAI).

BACKGROUND: Bicompartmental or unicompartmental knee arthroplasty (BKA, UKA) is currently advocated as an alternative solution to conventional total knee arthroplasty (TKA) in order to preserve bone stock and ligaments for limited osteoarthritis (OA) with intact anterior and posterior cruciate ligaments (ACL, PCL). However, the actual rate of UKA or BKA compared to TKA procedures in OA patients has not been reported. In this study, we retrospectively analyzed preoperative MRI of the knee in subjects who underwent knee arthroplasty and assessed the potential for UKA or BKA as an alternative treatment. METHODS: Data were extracted from the Osteoarthritis Initiative (OAI) public use data set, which included 4,796 subjects, ages 45-79. 3.0 Tesla MRI scanners were dedicated to imaging the knees of OAI participants annually from February 2004 to March 2010. Extensive quantitative measurements of the knee MRI were performed on 87 patients who underwent knee arthroplasty during follow-up visits. We assessed the cartilage thickness and defect size in the medial femorotibial joint (FTJ), lateral FTJ, and patellofemoral joint (PFJ) as well as ligamentous injury, bone marrow edema, and subchondral cyst size from 2D coronal turbo spin echo (TSE), 2D sagittal TSE, 3D coronal T1-weighted water-excitation fast low angle shot (FLASH), and 3D sagittal water-excitation double echo steady-state (DESS) with axial and coronal reformat images. RESULTS: Eighty-five subjects (97.7%) were subjected to TKA, while only 2 subjects (2.3%) received UKA from the OAI database. Based on the preoperative MRI findings criteria, 51 of 87 subjects (58.6%) met the indication for TKA including the 2 UKA subjects above. This rate was significantly lower (p<0.001) than the actual TKA rate received. Among 85 subjects who actually underwent TKA, 31 subjects (36.5%) and 5 subjects (5.9%) met the indication for BKA and UKA, respectively. CONCLUSIONS: Many medial or lateral compartmental OA subjects, with or without patellar compartment defects have undergone TKA. The results of this study suggest the indication for partial arthroplasty, such as UKA or BKA, may increase when cartilage in each compartment, as well as ligaments and subchondral bone status are comprehensively evaluated.

Predictors of delayed-stage colorectal cancer: are we neglecting critical demographic information?

PURPOSE: We sought to distinguish roles of demographic variables and bowel segments as predictors of delayed versus early stage colorectal cancer in California. METHODS: Demographic and anatomic variables for 66,806 colorectal cancers were extracted from the California Cancer Registry for 2004-2008 and analyzed using logistic regression as delayed versus early stage. RESULTS: Odds ratios (OR) for binary stage categories comparing age <40 (OR=2.58; 95% CI=2.26-2.94), 40-49 (1.71; 95%=1.60-1.83) and 75+ (1.05; 1.02-1.09) relative to 50-74 years were computed. Compared with non-Hispanic whites, ORs for stage categories were: 1.05; 0.99-1.13 (non-Hispanic blacks), 1.08; 1.02-1.13 (Hispanics), and 1.05; 1.00-1.10 (Asian/others). Females had higher odds of delayed diagnosis (1.09; 1.06-1.13) than males. Descending ORs were measured for successively lower to highest socioeconomic status (SES) quintiles (OR 4:5=1.08; 1.03-1.14, OR 3:5=1.13; 1.08-1.19, OR 2:5=1.18; 1.12- 1.24, and OR 1:5=1.21; 1.14-1.28). CONCLUSIONS: Younger and older than age 50-74; females; Hispanic ethnicity; bowel segment contrasts (right/left, proximal/distal, cecum plus appendix/distal), and lower SES were independent predictors of delayed diagnosis. Low SES was the most robust predictor of delayed diagnosis, independent of other covariates. Approximately 77% of delayed diagnoses were in non-Hispanic whites and Asian/others. These findings illustrate the value of a community SES index for targeting egalitarian colorectal cancer screening.

Interaction of the tyrosine phosphatase SHP-2 with Gab2 regulates Rho-dependent activation of the c-fos serum response element by interleukin-2.

Gab2 (Grb2-associated binder-2), a member of the IRS (insulin receptor substrate)/Gab family of adapter proteins, undergoes tyrosine phosphorylation in response to cytokine or growth factor stimulation and serves as a docking platform for many signal transduction effectors, including the tyrosine phosphatase SHP-2 [SH2 (Src homology 2)-domain-containing tyrosine phosphatase]. Here, we report that, following IL-2 (interleukin-2) stimulation of human T lymphocytes, SHP-2 binds tyrosine residues 614 and 643 of human Gab2 through its N- and C-terminal SH2 domains respectively. However, the sole mutation of Tyr-614 into phenylalanine is sufficient to prevent Gab2 from recruiting SHP-2. Expression of the Gab2 Tyr-614-->Phe (Y614F) mutant, defective in SHP-2 association, prevents ERK (extracellular-signal-regulated kinase) activation and expression of a luciferase reporter plasmid driven by the c-fos SRE (serum response element), indicating that interaction of SHP-2 with Gab2 is required for ERK activation in response to IL-2. Further investigation of IL-2-dependent induction of SRE showed that expression of a constitutively active mutant of the RhoA GTPase synergizes with IL-2 for SRE-driven transcription, whereas a dominant-negative mutant reduces the IL-2 response. Thus, in response to IL-2, full induction of the SRE requires ERK-dependent as well as Rho-dependent signals that target the Ets-box and the CArG-box respectively. We also report that the synergy between Gab2/SHP-2 and RhoA for IL-2-dependent CArG-box-driven transcription depends upon MEK (mitogen-activated protein kinase/ERK kinase) activation, and is likely to involve regulation of the serum response factor co-activator MAL. Our studies thus provide new insights into the role of Gab2 and SHP-2 in IL-2 signal transduction.